Artículo

Iacaruso, M.F.; Galli, S.; Martí, M.; Villalta, J.I.; Estrin, D.A.; Jares-Erijman, E.A.; Pietrasanta, L.I. "Structural model for p75 NTR-TrkA intracellular domain interaction: A combined FRET and bioinformatics study" (2011) Journal of Molecular Biology. 414(5):681-698
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Abstract:

Nerve growth factor (NGF) is a member of the neurotrophins, which are important regulators of embryonic development and adult function in the vertebrate nervous systems. The signaling elicited by NGF regulates diverse activities, including survival, axon growth, and synaptic plasticity. NGF action is mediated by engagement with two structurally unrelated transmembrane receptors, p75 NTR and TrkA, which are co-expressed in a variety of cells. The functional interactions of these receptors have been widely demonstrated and include complex formation, convergence of signaling pathways, and indirect interaction through adaptor proteins. Each domain of the receptors was shown to be important for the formation of TrkA and p75 NTR complexes, but only the intramembrane and transmembrane domains seemed to be crucial for the creation of high-affinity binding sites. However, whether these occur through a physical association of the receptors is unclear. In the present work, we demonstrate by Förster resonance energy transfer that p75 NTR and TrkA are physically associated through their intracellular (IC) domains and that this interaction occurs predominantly at the cell membrane and prior to NGF stimulation. Our data suggest that there is a pool of receptors dimerized before NGF stimulus, which could contribute to the high-affinity binding sites. We modeled the three-dimensional structure of the TrkA IC domain by homology modeling, and with this and the NMR-resolved structure of p75 NTR, we modeled the heterodimerization of TrkA and p75 NTR by docking methods and molecular dynamics. These models, together with the results obtained by Förster resonance energy transfer, provide structural insights into the receptors' physical association. © 2011 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Structural model for p75 NTR-TrkA intracellular domain interaction: A combined FRET and bioinformatics study
Autor:Iacaruso, M.F.; Galli, S.; Martí, M.; Villalta, J.I.; Estrin, D.A.; Jares-Erijman, E.A.; Pietrasanta, L.I.
Filiación:Centro de Microscopías Avanzadas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina
Departamento de Química Orgánica, Universidad de Buenos Aires, CONICET, C1428EHA Buenos Aires, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas, C1033AAJ Buenos Aires, Argentina
Departamento de Química Biológica, Analítica y Química Física/INQUIMAE, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina
Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom
Departamento de Fisiologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina
Palabras clave:heterodimerization; molecular dynamics; NGF receptors; physical association; structural model; adaptor protein; nerve growth factor; nerve growth factor receptor; neurotrophin receptor p75; protein tyrosine kinase A; animal cell; article; binding site; bioinformatics; cell membrane; complex formation; controlled study; dimerization; fluorescence resonance energy transfer; molecular dynamics; nonhuman; nuclear magnetic resonance spectroscopy; priority journal; protein domain; protein protein interaction; protein structure; signal transduction; Animals; Computational Biology; Fluorescence Resonance Energy Transfer; Hippocampus; Mice; Nerve Growth Factor; PC12 Cells; Protein Binding; Protein Interaction Domains and Motifs; Rats; Receptor, Nerve Growth Factor; Receptor, trkA; Structural Homology, Protein; Vertebrata
Año:2011
Volumen:414
Número:5
Página de inicio:681
Página de fin:698
DOI: http://dx.doi.org/10.1016/j.jmb.2011.09.022
Título revista:Journal of Molecular Biology
Título revista abreviado:J. Mol. Biol.
ISSN:00222836
CODEN:JMOBA
CAS:nerve growth factor, 9061-61-4; Nerve Growth Factor, 9061-61-4; Receptor, Nerve Growth Factor; Receptor, trkA, 2.7.10.1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222836_v414_n5_p681_Iacaruso

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Citas:

---------- APA ----------
Iacaruso, M.F., Galli, S., Martí, M., Villalta, J.I., Estrin, D.A., Jares-Erijman, E.A. & Pietrasanta, L.I. (2011) . Structural model for p75 NTR-TrkA intracellular domain interaction: A combined FRET and bioinformatics study. Journal of Molecular Biology, 414(5), 681-698.
http://dx.doi.org/10.1016/j.jmb.2011.09.022
---------- CHICAGO ----------
Iacaruso, M.F., Galli, S., Martí, M., Villalta, J.I., Estrin, D.A., Jares-Erijman, E.A., et al. "Structural model for p75 NTR-TrkA intracellular domain interaction: A combined FRET and bioinformatics study" . Journal of Molecular Biology 414, no. 5 (2011) : 681-698.
http://dx.doi.org/10.1016/j.jmb.2011.09.022
---------- MLA ----------
Iacaruso, M.F., Galli, S., Martí, M., Villalta, J.I., Estrin, D.A., Jares-Erijman, E.A., et al. "Structural model for p75 NTR-TrkA intracellular domain interaction: A combined FRET and bioinformatics study" . Journal of Molecular Biology, vol. 414, no. 5, 2011, pp. 681-698.
http://dx.doi.org/10.1016/j.jmb.2011.09.022
---------- VANCOUVER ----------
Iacaruso, M.F., Galli, S., Martí, M., Villalta, J.I., Estrin, D.A., Jares-Erijman, E.A., et al. Structural model for p75 NTR-TrkA intracellular domain interaction: A combined FRET and bioinformatics study. J. Mol. Biol. 2011;414(5):681-698.
http://dx.doi.org/10.1016/j.jmb.2011.09.022